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BACKGROUND Congenital heart defects (CHDs) are the most common major malformations in newborns. In this study we examined the associations between the occurrence of CHDs in children and periconceptional occupational parental exposures to chemicals. METHODS In an age-matched case–control study with standardized data collection at c. 15 months after birth, 424 mothers and 421 fathers of a child with CHD and 480 mothers and 477 fathers of a non-malformed child, filled out questionnaires on periconceptional general and job characteristics. A job exposure matrix, which links the information on job title and a description of work tasks to an expert judgement on exposure to chemicals in the workplace, was used. RESULTS The overall prevalence of occupational exposure to chemicals was 5.0 in cases and 6.2% in controls for mothers [odds ratio (OR) adjusted = 0.92; 95% confidence interval (CI): 0.26–3.25], while 22.3 and 15.9% for fathers, respectively (OR adjusted = 1.23; 95% CI: 0.39–3.91). No association of maternal occupational exposure to chemicals with risk of CHDs was found. Paternal exposure to phthalates was associated with a higher incidence of CHDs in general (OR adjusted = 2.08; 95% CI: 1.27–3.40). Paternal exposure to phthalates was associated with perimembranous ventricular septal defect (OR adjusted = 2.84; 95% CI: 1.37–5.92), to polychlorinated compounds with atrioventricular septal defect (OR adjusted = 4.22; 95% CI: 1.23–14.42) and to alkylphenolic compounds with coarctation of the aorta (OR adjusted = 3.85; 95% CI: 1.17–12.67). CONCLUSIONS Periconceptional paternal (but not maternal) occupational exposure to certain chemicals is associated with an increased risk of CHDs in children. The results, however, must be interpreted cautiously as exposure probabilities are a crude measure of exposure. [ABSTRACT FROM PUBLISHER]

Background: Derangements in the maternal methylation pathway, expressed by global hypomethylation and hyperhomocysteinemia, are associated with the risk of having a child with a congenital heart defect (CHD). It is not known whether periconception exposure to these metabolic derangements contributes to chromosome segregation and metabolic programming of this pathway in the foetus. Design: In a Dutch population-based case–control study of 143 children with CHD and 186 healthy children, we investigated S- adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), total homocysteine (tHcy), the vitamins folate and B12 and the functional single nucleotide polymorphisms in the folate gene MTHFR 677C>T and 1298A>C. Comparisons were made between cases and controls adjusting for age, medication, vitamin use and CHD family history. Results: In the overall CHD group, the median concentrations of SAM (P = 0Æ011), folate in serum (P = 0Æ021) and RBC (P = 0Æ030) were significantly higher than in the controls. Subgroup analysis showed that this was mainly attributable to complex CHD with higher SAM (P < 0Æ001), SAH (P = 0 Æ012) and serum folate (P = 0Æ010) independent of carriership of MTHFR polymorphisms. Highest concentrations of SAM, SAH and folate RBC were observed in complex syndromic CHD. The subgroup of children with Down syndrome, however, showed significantly higher SAH (P = 0Æ037) and significantly lower SAM:SAH ratio (P = 0Æ034) compared with other complex CHD, suggesting a state of global hypomethylation. Conclusion:High concentrations of methylation biomarkers in very young children are associated with complex CHD. Down syndrome and CHD may be associated with a global hypomethylation status, which has to be confirmed in tissues and global DNA methylation in future studies. [ABSTRACT FROM AUTHOR]